Induction of cell-mediated immunity to autologous melanoma cells and regression of metastases after treatment with a melanoma cell vaccine preceded by cyclophosphamide

There is considerable evidence in animal tumor systems that antitumor immunity is modulated by suppressor T-lymphocytes, and that the cytotoxic drug cyclophosphamide (CY) can abrogate that suppression. We measured the acquisition of delayed-type hypersensitivity (DTH) to autologous melanoma cells in...

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Bibliographic Details
Published inCancer research (Chicago, Ill.) Vol. 46; no. 5; pp. 2572 - 2577
Main Authors BERD, D, MAGUIRE, H. C. JR, MASTRANGELO, M. J
Format Journal Article
LanguageEnglish
Published Philadelphia, PA American Association for Cancer Research 01.05.1986
Subjects
Adult
Antineoplastic agents
Biological and medical sciences
Chemotherapy
Cyclophosphamide - administration & dosage
Female
Humans
Hypersensitivity, Delayed - immunology
Immunity, Cellular
Immunotherapy
Liver Neoplasms - secondary
Male
Medical sciences
Melanoma - immunology
Melanoma - therapy
Middle Aged
Neoplasm Metastasis
Pharmacology. Drug treatments
Vaccines - immunology
Antineoplastic agent
Skin disease
Regression
Cellular immunity
Vaccine
Metastasis
Active immunization
Chemotherapy
Immunotherapy
Malignant melanoma
Tumor
Skin
Combined treatment
Tumor cell
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Summary:There is considerable evidence in animal tumor systems that antitumor immunity is modulated by suppressor T-lymphocytes, and that the cytotoxic drug cyclophosphamide (CY) can abrogate that suppression. We measured the acquisition of delayed-type hypersensitivity (DTH) to autologous melanoma cells in 19 patients with metastatic malignant melanoma. The patients were treated with an autologous melanoma cell vaccine, either given alone, or given 3 days after the administration of CY, 300 mg/m2 i.v. The DTH responses of CY-pretreated patients were significantly greater than those of control (vaccine only) patients. Thus, after two vaccine treatments, the median DTH responses (mm induration) were as follows: controls, 4 mm; CY pretreated, 11 mm; P = 0.034, Mann-Whitney U test, 2-tailed. Whereas seven of eight CY-pretreated patients developed DTH to autologous melanoma cells of at least 5 mm, only two of seven controls did so (P = 0.034, Fisher's exact test). Two patients had significant antitumor responses to treatment with CY plus vaccine, consisting of complete disappearance of skin metastases and a pulmonary nodule in one, and regression of s.c. and liver metastases in the other. Both patients remain free of melanoma after 42 and 33 mo, respectively.
ISSN:0008-5472
1538-7445